title: Solid-phase synthesis of tris-benzamides as α-helix mimetics.
abstract: Small molecules mimicking α-helices are of great interest since numerous protein-protein interactions use helical structures at the interface. With a goal of generating libraries of α-helix mimetics, an efficient solid-phase synthetic method was developed to produce tris-benzamides. The tris-benzamide scaffold was designed to place three side-chain functional groups found at the i, i + 4, and i + 7 positions of an α-helix, emulating one helical face. The synthetic strategy involves simple and iterative reactions of removal of an allyl ester, formation of an amide bond via an O → N acyl migration, and an O-alkylation. A small library of twenty tris-benzamides containing a variety of functional groups was prepared in high purity (83-99%) to demonstrate the versatility of the synthetic approach. This methodology allowed the facile and rapid construction of α-helix mimetics that would facilitate the identification of small molecules for target proteins.
authors.affiliation: Department of Chemistry, University of Texas at Dallas, Richardson, TX 75080, United States.
authors.forename: Tae-Kyung
authors.initials: TK
authors.lastname: Lee
authors.forename: Jung-Mo
authors.initials: JM
authors.lastname: Ahn
mesh_terms: D001549:Benzamides / Q000138:chemical synthesis / Q000737:chemistry*; D032701:Biomimetics; D020650:Combinatorial Chemistry Techniques; D015394:Molecular Structure; D011485:Protein Binding; D017433:Protein Structure, Secondary; D011506:Proteins / Q000737:chemistry*
chemical_list: D001549:Benzamides; D011506:Proteins